Previous studies from our laboratory indicate that the measurement of total glycosylated serum protein (TGSP) is clinically feasible, is correlated with mean preprandial blood glucose concentration of the previous seven days, and may be an indicator of glucose intolerance. We now propose to extend our orignial studies to determine the half lives of albumin and glycosylated albumin in normal and diabetic animals. Only recently have studies indicated an effect of diabetes on protein homeostasis; and little is known about serum protein degradation in diabetes mellitus. Our studies as well as studies of Hemoglobin A1 (HbA1) suggest that the degradation of these proteins in diabetes may be accelerated. Secondly, we wish to assess the concentration of glycosylated blood proteins at various stages of pregnancy in normal, glucose intolerant and diabetic subjects and to determine whether TGSP or HbA1 are correlated with fetal or maternal outcome. TGSP has not been studied in pregnancy and it offers advantages over HbA1, the clinical utility of which remains uncertain. Thirdly, we wish to investigate acetylator polymorphism as one possible determinant of nonenzymatic protein glycosylation. This genetic dimorphism has been associated with diabetes and possibly with the development of diabetic microvascular disease. A possible mechanism for a relation of acetylator status or serum protein glycosylation is offered by the inhibition of albumin glycosylation by aspirin, which acetylates the lysine 198 residue in a highly specific reaction. Ip serum protein glycosylation is correlated with acetylator status, a diabetic population at increased risk for microvascular disease might be identified.